Recently we demonstrated that changes in 5-HTlA+B- and 5-HT1B- in addition to S2-receptor binding sites are associated with an increase in 5-HT release and circulation of water after ischemia and microcirculaticn. This study represents a continuous effort in elucidation of the mechanisms involved in formation and progression of ischemic cerebral edema. The investigations focused on the effect of ischemia on the "fluidity" of the cerebro-cortical membranes and its susceptibility to lipid peroxidation in vitro. An increased membrane "fluidity" was demonstrated by a decreased fluorescence anisotropy after ischemia and reflow but not by ischemia alone. At the same time the susceptibility of the membrane to lipid peroxidation in vitro was lower than that seen in either controls or after ischemia alone. These results together with the previous findings demonstrating changes in S2-, 5-HTlA+B and 5-HTlB receptor binding sites in the synaptosomes indicate that the cerebro-cortical membranes are more severly affected during recirculation than in ischemia.